The euphorogenic and addictive properties of cocaine are believed to be mediated by this drug's blockade of the dopamine (DA) transporter. This multimeric protein is located on the terminals of DA neuronal projections and functions to remove DA from the synapse back into the terminal for either metabolism or recycling. We have developed a promising probe of the DA transporter, [123I]beta-CIT (2beta-carbomethoxy-3beta-(4- iodophenyl)tropane), which can be safely used to quantify the levels of DA transporters in the living human brain with SPECT (single photon emission computed tomography). We propose SPECT imaging with [123I]beta-CIT in patients with cocaine addiction to determine whether current drug usage is associated with an upregulation of DA transporters and whether abstinence is associated with a decrease towards control values. Postmortem studies have reported 50-100% increases in DA transporters in cocaine addicts. Our preliminary SPECT [123I]beta-CIT study of 4 cocaine addicts have shown a 35% increase in comparison to 4 age-matched healthy subjects. We propose to study a larger sample of subjects to examine this phenomenon more thoroughly. Animal studies of chronic cocaine administration suggest that the dosage of cocaine and gender may affect the levels of DA transporters. Thus, we propose to study equal sized groups of males and females and to correlate the DA transporter levels with cocaine usage prior to study. Our pilot study of 4 cocaine addicts during abstinence have shown about 17% decrease during 2-4 weeks of abstinence. We propose to study a larger sample of subjects over a longer period of time and to examine the potential correlation of the number and rate of change of transporters with craving and relapse. Euphoria, craving, and relapse may well be related to the levels of synaptic DA, which are modulated in part by this presynaptic DA transporter. If chronic cocaine usage causes an increase in the number of DA transporters, then early abstinence would presumably be associated with a target site in the brain for cocaine (i.e., the DA transporter) may provide a valuable biological marker to help elucidate neurochemical correlates of addiction, craving, and relapse.